Long-term objectives of our study are to reduce morbidity and mortality from congenital Toxoplasma gondii infection by improved use of antimicrobial agents and understanding pathogenesis of this disease. Hypotheses are that treatment of congenital toxoplasmosis during the first year of life will improve outcome into the second decade of life, treatment will not be associated with late toxicities and that understanding natural history and pathogenesis can improve medical management of this disease. The first specific aim is to determine optimal methods to evaluate, treat, and provide follow up care for children suffering from congenital toxoplasmosis. Pre-specified outcomes of the Chicago-based, National Collaborative Congenital Toxoplasmosis Study (NCCCTS) cohort of infected and treated children from childhood into adolescence and early adulthood, will be determined. Cognitive, motor, ocular and audiologic outcome will be determined following treatment with one of two dosages of pyrimethamine plus sulfadiazine during the first year of life. Evaluation of an NCCCTS cohort of older, untreated "historical patients" with retinal disease provides an opportunity to determine natural history of patients with congenital infection detected after the first year of life. Our work also will be extended to determine efficacy of a Public Health Program in prevention of adverse outcomes from this disease. The New England Newborn Screening Program (NENSP) developed a Public Health Program of newborn screening for congenital toxoplasmosis with treatment for affected infants during their first year of life. First (1987-1993), they used a lower and then (1993-97), a higher dosage of medicines. These initially asymptomatic children (80% with no retinal lesions noted at birth) were diagnosed as newborns in Massachusetts and New Hampshire and treated for 1 year. They will have a vision, retina and hearing screen when they are in their second decade of life. This will be performed collaboratively by Massachusetts and NCCCTS specialist physicians, so that evaluations of these outcomes will be standardized, uniform and directly comparable with evaluations for the NCCCTS cohorts. The second specific aim uses sera from these NCCCTS clinically well-characterized individuals with congenital toxoplasmosis and their mothers to determine whether clinical outcomes are influenced by clonal type of parasite, mode of maternal acquisition of the parasite (which might correlate with inoculum size or initial immune response), or presence of antibody directed at glycosylinositolphospholipids of the parasite. These studies will contribute to determining how to best provide medical care to children and young adults afflicted with congenital toxoplasmosis and to better understanding pathogenesis of this disease. [unreadable] [unreadable] [unreadable]